International Journal of Infectious Diseases 32 (2015) 68–75

Contents lists available at ScienceDirect

International Journal of Infectious Diseases

journal homepage: www.elsevier.com/locate/ijid

Review

Health status and quality of life in tuberculosis

James Brown a,*, Santino Capocci a, Colette Smith b, Steve Morris c, Ibrahim Abubakar d,
Marc Lipman a
a
Centre for Respiratory Medicine, Royal Free London NHS Foundation Trust, London, and Division of Medicine, University College London, Pond Street, London
NW3 2QG, UK
b
Research Department of Infection and Population Health, University College London, London, UK
c
Department of Applied Health Research, University College London, London, UK
d
Research Department of Infection and Population Health, University College London, London, and Medical Research Council Clinical Trials Unit, London, UK

A R T I C L E I N F O S U M M A R Y

Article history: Tuberculosis (TB) is a leading cause of global morbidity, yet there is limited information regarding its
Received 17 November 2014 impact on quality of life and health status. This is surprising given the implications for patient care, the
Received in revised form 22 December 2014 evaluation of novel treatments or preventative strategies, and also health policy. Furthermore, there is no
Accepted 22 December 2014
validated TB-specific instrument that measures health status, and thus a wide and non-standardized
range of assessment tools have been employed. The studies to date have chosen a number of different
Keywords: comparator populations, and in many TB endemic areas there is a lack of normative data regarding the
Tuberculosis health status of the general population. Systematic evaluations of quality of life are urgently needed in
Quality of life
specific groups, including those with extrapulmonary TB, drug-resistant disease, HIV co-infection, and
Health status
latent TB infection, and in children with TB; the assessment of post-treatment disability is also required.
Health economics
Measures of health ß 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).

1. Introduction inaccurate, and can undermine the validity of cost-effectiveness

studies of TB management.
The suffering caused by tuberculosis (TB) has been acknowl- Impairment in HRQOL is a complex construct of influences
edged for millennia,1 though the systematic evaluation of health- including physical, mental, and social well-being3 – thus illness is
related quality of life (HRQOL) is a much more recent develop- experienced by individuals, yet cannot be understood indepen-
ment.2 TB is a leading cause of morbidity in many regions, and as dently of the societies in which people live.4 Although a biological
such an understanding of its effect on quality of life and health definition of TB infection (i.e., latent TB) or disease (active TB) may
status is important for patient care, the evaluation of novel be universal, it is not possible to produce a single numerical value
treatments or preventative strategies, and also for health policy, as that summarizes the impact of TB on an individual. It is not
data on quality of life are used within health economic evaluations. surprising, therefore, that quantitative studies have reported a
Several difficulties arise when assessing quality of life in TB: there wide range of values for the health impairment associated with TB
is no validated TB-specific instrument that measures health status, before, during, and after treatment.5 In this review we will
and there are difficulties in choosing appropriate comparator summarize the evidence regarding quality of life in TB, highlight
populations and a lack of normative data on health status for the areas where there is limited information available, and discuss its
general population in many TB endemic areas. Furthermore, there importance in relation to health economic evaluations.
are few systematic evaluations of quality of life in specific groups,
such as those with extrapulmonary TB, drug-resistant disease, HIV 2. Instruments used to measure health-related quality of
co-infection, and latent TB infection (LTBI), or in children with TB. life in TB
These make ‘health status’ summaries in TB difficult, probably
Evaluations of HRQOL can utilize generic tools applicable to
many conditions, or specific measures designed to evaluate a
* Corresponding author. Tel.: +44 207 317 7561. particular disease or organ system. Both strategies have advantages,
E-mail address: [email protected] (J. Brown). and a combination of generic and specific tools is often helpful.

http://dx.doi.org/10.1016/j.ijid.2014.12.045
1201-9712/ß 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 J. Brown et al. / International Journal of Infectious Diseases 32 (2015) 68–75 69

Many different instruments have been used to evaluate HRQOL in caused by anxiety or stigmatization, or the adverse effects of
TB, though none are designed specifically for TB (Table 1). medication.6
The choice of population against which to compare the HRQOL
in those with TB is important. TB often preferentially affects 3. Quality of evidence about quality of life in TB
disadvantaged groups or particular ethnic minorities, and hence
comparisons of HRQOL with those in the general population may Systematic reviews by Chang et al.,7 Guo et al.,8 and Bauer et al.5
be misleading. An ideal comparator group would be identical in provide an appraisal of the available evidence regarding quality of
all respects, other than the absence of TB. Those with LTBI life in those with TB. The most recent of these (which contains a
represent an attractive group for such comparisons, as they literature search up to April 2011) evaluates 38 articles describing
are likely to have similar backgrounds and hence cultural 28 unique study cohorts comprising 6028 patients. However,
understanding of illness, in particular TB, and by definition do assessment of the quality of the primary studies suggests that
not have symptoms of active disease. However a diagnosis of significant risks of bias may be present. In addition, the
LTBI may itself be associated with a reduction in health status psychometric properties of the instruments used are often not

Table 1
Instruments used to assess quality of life in TB

Name of instrument Comments

General quality of life instruments

Brief Disability Questionnaire (BDQ) 11-item scale; higher scores indicate worse HRQOL
Duke Health Profile (DUKE) 63 items evaluating symptoms and physical, social, and emotional function; higher scores indicate
better HRQOL
Dysfunctional Analysis Questionnaire (DAQ) 50 items evaluating social, vocational, personal, familial, and cognitive domains; higher scores
indicate worse HRQOL
Euro-QoL (EQ 5D) 5 domains each ranked with a 3-point scale; higher scores indicate better HRQOL
General Health Questionnaire 12 (GHQ 12) Modified version of the General Health Questionnaire 60. Each item ranked with a 4-point Likert
scale; higher scores indicate worse HRQOL
Health Utilities Index 2 (HUI 2) 7 items, each with 3 to 5 levels, used to calculate overall health utility function from 0 (death) to 1
(perfect health)
Health Utilities Index 3 (HUI 3) 8 items, each with 5 to 6 levels, used to calculate overall health utility function from 0 (death) to 1
(perfect health)
Life Satisfaction Index Z 13 items, total scores range from 0 to 26, with higher scores indicating better HRQOL
Present State Examination (PSE) Combined general health questionnaire and self-rating depression scale; higher scores indicate
worse HRQOL
SF-36 Health Survey (SF-36) 36 items covering physical and mental wellbeing. Scores from 0–100, with higher scores indicating
greater HRQOL
SF-12 Health Survey Abbreviated form of the SF-36
SF-6D utility score 11-item measure of health status. Scores range from 0 to 1.0, with higher scores indicating better
HRQOL
Sheehan Disability Scale (SDS) 20 items evaluating work, family, and social lives. Scores from 0 to 30; higher scores indicate worse
HRQOL
Sickness Impact Profile (SIP) 136 items evaluating personal and social impact of illness; a score of >10 indicates severe
dysfunction
Severe Respiratory Insufficiency Questionnaire (SRI) 49 items ranked with a 5-point Likert scale evaluating respiratory complaints and associated
physical and social limitations; higher scores indicate better HRQOL
Standard Gamble Subjects chose between a given health state and an imaginary gamble between possible outcomes
of perfect health and death; results are used to calculate a HRQOL score ranging from 0 to 1, with
higher scores indicating better HRQOL
Symptoms Check List (SCL-90) 90 items in 9 domains used to calculate three global indices of global severity index, positive
symptom total, and positive symptom distress index; higher scores indicate worse HRQOL
Visual Analogue Scale (VAS) Subjects mark on a scale where they rate their own health, either using a 10-cm scale (0 cm = death,
10 cm = perfect health) or a 100-cm ‘feeling thermometer’
World Health Organization’s Quality of Life–BREF 26 items comprising 5 domains (physical health, psychological health, social relationships,
(WHOQOL-BREF) environment) ranked on a 5-point Likert scale; higher scores indicate better HRQOL
Instruments assessing psychological morbidity
Beck Depression Inventory (BDI) 21-item questionnaire designed to evaluate depression; higher scores indicate more severe
depression, with a cut-off of 13 used to indicate depression
Beck Depression Inventory (BDI Short Form) 13-item questionnaire evaluating the presence of depression; overall score 0–3 = none or minimal
depression, 4– 7 = mild depression, 8–15 = moderate depression, 16 = severe depression
Hospital Anxiety and Depression Scale (HAD) 14 items evaluating anxiety and depression; higher scores indicate more anxiety/depression
Rosenberg Self-Esteem Scale (RSE) 10 items each with a 4-point scale evaluating self-esteem
Mood Adjective Check List Short Form (MACL) 38 items evaluating three psychological domains (pleasantness, activation, calmness)
Self-Rating Anxiety Scale (SAS) 20 items with a 4-point Likert scale evaluating anxiety; higher scores indicate worse HRQOL
Centre for Epidemiologic Studies Depression Scale (CES-D) 15 items each with a 4-point Likert scale; higher scores indicate more severe depression
Kessler 10 10 items assessing psychological distress, each with a 5-point Likert scale; higher scores indicate
better HRQOL
State-Trait Anxiety Inventory Short Form (STAI-6) 6 items with a 4-point scale used to evaluate anxiety
Disease or system-specific instruments
St. George Respiratory Questionnaire Short Form (SGRQ) 50 items in 3 domains (symptoms, activity, and impacts) specific to respiratory illnesses and
originally developed to assess patients with airways disease
World Health Organization’s Quality of Life – HIV Modified version of the WHOQOL-100 used for patients with HIV; higher scores indicate better
(WHOQOL-HIV) HRQOL
DR-12 TB-specific quality of life score with 12 items each ranked on a scale of 1–3; higher scores indicate
better HRQOL
MOS-HIV 35-item questionnaire validated to assess quality of life in HIV-infected individuals

HRQOL, health-related quality of life.

70 J. Brown et al. / International Journal of Infectious Diseases 32 (2015) 68–75

fully evaluated; for instance only a minority of studies describes of life for those with TB. Most give cross-sectional data only, and
ceiling and floor effects in the instruments used (i.e., that a very many do not include a comparator population (Table 2).63–70
large proportion of respondents have the highest or lowest Instruments differ in the dimensions used, with some evaluating
possible response to a particular variable), and where they do, physical health, some specifically measuring psychological mor-
significant effects are noted: for instance over 50% of those with bidity, and others attempting a holistic assessment of HRQOL.
concurrent or previous TB reported the highest scores for five of the Therefore, different instruments evaluate different effects of TB.
SF-36 subscales in the study by Dion et al.9 Studies that utilize instruments such as the SF-36 that include both
Bias by language of patients may be a significant issue in physical and psychological domains, confirm that significant
evaluating quality of life, particularly in settings where subjects deficits in psychological wellbeing exist alongside physical
come from diverse migrant populations.10 Several studies were complaints. This is also reported by a number of other
only able to assess patients who spoke the language of the studies.8,14–17,25
investigators – for instance of 411 charts screened for potential When active TB is compared to a comparator population, the
inclusion in a study from Canada, one-third were excluded because evidence suggests that active TB is associated with a lower health
of their inability to speak English or French.11 Similarly, the study status than found in subjects without TB or with LTBI. For example,
of Kruijshaar and Abubakar only included those who spoke Guo et al. described the difference in SF-36 scores between those
adequate English, and although the number of patients unable to with latent and active TB in Canada and found a worse mean
participate because of language barriers is not described, the Physical Component Summary (PCS) score of 44.8 and Mental
authors comment that selection bias could have occurred.12 Component Summary (MCS) score of 40.1 in those with active TB,
The use of written self-administered questionnaires raises compared to a mean PCS score of 54.7 and MCS score of 50.3 in
difficulties where subjects do not have sufficient literacy and may those with latent TB.8
introduce bias from varied levels of reading comprehension. There is less information available about longitudinal changes
Pasipanodya et al. therefore chose to administer the St. Georges in health status with treatment (Table 3). Only two studies (one
Respiratory Questionnaire (SGRQ) by reading translations of the from the UK and the other from Canada) provide data from
questionnaire in the language of the subject.13 Although this deals developed countries, in which TB primarily affects migrant
with the difficulty of reading comprehension bias, the SGRQ has populations. The study by Kruijshaar et al.18 in the UK followed
not been validated as an interviewer-administered tool and may patients at diagnosis and at 2 months, and the study by Marra et al.
yield different results when used this way. in Canada assessed patients at diagnosis and at 6 months.19 Both
used the SF-36 alongside other instruments and both identified
4. Health status impairment associated with TB and the effect improvements in quality of life with treatment – although in
of treatment neither case was the improvement sufficient to reach population
norms. Kruijshaar et al. assessed the change between baseline and
At least 40 different papers from 16 countries (primarily in the 2 months and reported only a small improvement in the PCS score
developing world) provide information on health status or quality of the SF-36 (36 to 39 points; p = 0.167), but a greater improvement

Table 2
Studies providing cross-sectional data

Author [Ref.] Year Location HRQOL assessment Site of disease Number Number Number of % HIV-positive
published instrument useda with with healthy
active TB latent TB controls

Westaway [16] 1992 South Africa Abbreviated BDI, RSE Pulmonary 100 0 0 Not stated
Wang [63]b 1998 China SF-36, QLI, KPS Pulmonary 228 0 228 Not stated
Aghanwa [17] 1998 Nigeria GHQ-30 Pulmonary 53 0 40 Not stated
Bhatia [64] 2000 India DAQ Not stated 50 0 0 Not stated
Aydin [15] 2001 Turkey GHQ-12 Pulmonary 119 0 38 Not stated
Yang [65]b 2003 China SCL-90 and Social Support Pulmonary 132 0 71 Not stated
Rating Scale (SSRS)
Dion [11] 2004 Canada VAS and Standard Gamble Not stated 17 25 0 All HIV-negative
Vinaccia [66]b 2007 Colombia SF-36 Pulmonary 60 0 0 Not stated
Pasipanodya [13] 2007 USA SGRQ Pulmonary 105 207 0 9.6% HIV-positive
Muniyandi [33] 2007 India SF-36 Pulmonary and 436 0 0 Not stated
extrapulmonary
Guo [8] 2008 Canada SF-36, HUI2/3, and a general Not stated 84 78 0 Not stated
health VAS
Unalan [67] 2008 Turkey SF-36, BDI Not stated 196 196 Not stated
Husain [68] 2008 Pakistan HAD, Illness Perception Not stated 108 0 0 Not stated
Questionnaire
Dhuria [69] 2009 India WHOQOL-BREF (Hindi version) Not stated 90 0 90 Not stated
Babikako [37] 2010 Uganda 35-item MOS instrument, VAS Pulmonary 133 0 0 50% HIV-positive
Chung [70] 2012 Taiwan Taiwan short version of the Pulmonary 140 0 130 Not stated
WHOQOL-BREF
Godoy [45] 2012 Brazil Asthma Questionnaire 20 Score Pulmonary, 18 0 0 All HIV-negative
MDR TB
Louw [41] 2012 South Africa SF-12 Not stated 4900 0 0 60% HIV-positive
Masumoto [14] 2014 Philippines Short Form-8, Duke-UNC Pulmonary 561 0 0 Not stated
Functional Social Support
Questionnaire, and
Medical Research Council
(MRC) dyspnoea scale

HRQOL, health-related quality of life; TB, tuberculosis; VAS, visual analogue scale; MDR, multidrug-resistant.
a
For details of the instruments used, see Table 1.
b
Full text not available in English, or only published in abstract form.
 J. Brown et al. / International Journal of Infectious Diseases 32 (2015) 68–75 71

Table 3
Studies providing prospective follow-up

Author [Ref.] Year Site Time-points Scales used Site of disease Number Number Number of HIV status
published assessed with with healthy
active TB latent TB controls

Chamla [25] 2004 China Baseline, 2 months, SF-36 Pulmonary and 102 0 103 Not stated
end of treatment extrapulmonary
Rajeswari [20] 2005 India 2 months and 6 months SF-36 Not stated 610 0 0 Not stated
Marra [19] 2008 Canada Baseline, 3 months, SF-36 and the BDI Pulmonary and 104 102 0 8% HIV-positive
and 6 months extrapulmonary
Maguire [24] 2009 Indonesia Baseline, 2 months, Modified SGRQ Pulmonary 115 0 0 4.50% HIV-positive
and 6 months
Kruijshaar [18] 2010 UK Diagnosis and 2 months SF-36 and EQ-5D Pulmonary and 61 0 0 Not stated
extrapulmonary
Bauer [6]b 2012 Canada Treatment initiation SF-36, Standard Pulmonary and 60 118 106 Not stated
and 2 months Gamble extrapulmonary
Deribew [39] 2013 Ethiopia Baseline and 6 months WHOQOL-HIV Not stated 124 0 465 All HIV-positive
Atif [26] 2014 Malaysia Baseline, end of SF-36 Pulmonary 216 0 0 All HIV-negative
intensive phase,
end of treatment

TB, tuberculosis.
a
For details of the instruments used, see Table 1.
b
Only published as abstract.

in MCS score (42 to 50 points; p = 0.003), which was associated Differences in treatment strategies vary considerably between
with a reduction in rates of anxiety and depression.18 Marra et al. health systems in ways that may affect quality of life. For instance
reported a mean 10-point difference in SF-36 MCS and 6.4-point the majority of patients treated in Germany are initially hospital-
difference in PCS between those with active and latent TB, which ized (with an average length of stay of 30 days in 201128), whilst in
narrowed to differences of 3.71 for MCS and 4.3 for PCS by the UK clinical guidelines advise against routine hospital admis-
6 months.19 sion.29 Although supervised therapy is strongly advocated by the
Studies from India,20–23 Indonesia,24 China,25 and Malaysia26 World Health Organization directly observed therapy strategy
provide data on changes in quality of life with treatment for TB in (WHO DOTS)30 and might improve quality of life by improving
the TB endemic areas. Again, such studies demonstrate improve- outcomes, it may also make employment more difficult or enhance
ments, but show residual deficits in quality of life and health status stigmatization. The use of ambulatory care is encouraged in
compared to those with latent TB, those without TB, or population current guidelines for the management of multidrug-resistant
norms. Atif et al. studied 216 individuals with pulmonary TB in (MDR)-TB,31 although its effect on quality of life is unknown.
Malaysia and reported an improvement in PCS score from 41.9 at Very little information is available regarding the long-term
baseline to 46 after 6 months, with an improvement in MCS from quality of life of those who have completed TB treatment and none
39.9 to 46.8.26 Maguire et al. described changes in health status of the studies that collected longitudinal data during TB treatment
using a modified SGRQ in 115 patients with smear-positive included follow-up post treatment completion. Pasipanodya et al.
pulmonary TB in Indonesia. The participants had a mean SGRQ documented respiratory symptoms using the SGRQ in 100 subjects
score of 45.4 at baseline, and 94% had an improvement of at least with pulmonary TB who had completed at least 20 weeks of TB
4 points (considered the minimum clinically important difference treatment in Texas, with the aim of evaluating pulmonary
in the SGRQ) by 2 months of treatment. Eighty percent had further impairment after TB; they noted a significant increase in SGRQ
significant improvement between 2 months and 6 months.24 score (i.e., worse health status) compared to those with latent TB.13
Subjects with the greatest deficits in lung function had higher
SGRQ scores (indicating greater impairment).
5. Exploring the causes of impaired health status Although TB can be associated with the development of long-
term complications (including bronchiectasis, airflow obstruction,
Qualitative research methodologies may provide insight into and restrictive pulmonary function deficits in the case of
the experiences of those with TB and illuminate causes of reduced pulmonary TB), the long-term effect of these changes on quality
quality of life. For example a study from Brazil conducted of life has not been assessed, and cost-effectiveness studies have
interviews with patients who had completed TB treatment to often assumed a return to normal quality of life on completion of
determine life experiences with TB.27 This demonstrated signifi- TB treatment.32 Although an assessment of SF-36 scores 1 year
cant levels of anxiety and stigmatization, which were in part after TB treatment in India did in fact suggest scores were
heightened by inaccurate beliefs concerning the aetiology and comparable with population norms,33 this is likely to be
transmissibility of TB. Studies evaluating the impact of TB on inaccurate, and conflicts with other data.34
quality of life have focused on assessments made whilst
individuals are on treatment. This neglects the impact at other
stages of disease – for instance those with TB may have symptoms 6. Quality of life in specific groups
for several months prior to diagnosis. Also, in addition to physical
and psychological harm, individuals can encounter stigmatization Estimating how much TB impacts on quality of life is essential
and social isolation. Once diagnosed, the adverse effects of anti-TB for analyses of cost effectiveness. However, it is responsible for a
medication can be considerable. In addition, individuals may face diverse variety of clinical problems – each of which may have a
extra costs accessing care and obtaining medication whilst variable impact on the affected individual. We consider the current
experiencing loss of employment. When treatment is completed, evidence regarding health status in adults with latent TB,
many can have long-term physical sequelae of TB, which in some extrapulmonary TB, drug-resistant TB, and HIV–TB co-infection,
cases result in life-long impairment (and further stigma). and the impact of TB on children.
72 J. Brown et al. / International Journal of Infectious Diseases 32 (2015) 68–75

6.1. Latent TB the authors did not appear to evaluate or account for the impact of
ART on quality of life in those with HIV–TB co-infection.
Health status and the effect of treatment for LTBI is important, Deribew et al. studied 124 HIV-positive individuals with TB and
as the population at risk is many times larger than that with active 465 without TB in Ethiopia using an Amharic version of the World
TB, and successful strategies to reduce the global burden of TB may Health Organization Quality of Life Instrument for HIV-infected
need to greatly increase rates of latent TB treatment.35 people.38,39 Those with HIV–TB demonstrated greater improve-
Those with latent infection by definition do not have symptoms ments in quality of life after 6 months of follow-up: in those with
associated with TB, yet by being given a diagnostic label may feel TB, scores for the physical health domain improved by a mean of
social stigmatization or anxiety. Furthermore, treatment can result 5.1 points, compared to a mean 0.7 points in subjects with HIV
in adverse events with no perceived short-term benefit to the alone. However those selected as controls were drawn from a
patient (beyond a potential reduction in anxiety about TB after clinically stable HIV population and were taking antiretrovirals.
completing treatment). The harms of diagnosis and treatment of Hence, in contrast to the HIV–TB patients, they are unlikely to have
LTBI must be balanced against the benefits of a reduced incidence had much in the way of change in their quality of life over time. The
of active TB. It should be noted that Bauer et al. found a reduction in strongest predictor of reduced quality of life was the presence of
HRQOL associated with LTBI treatment compared to healthy mental health issues (assessed by the Kessler 10 scale). Once more,
controls.6 Unfortunately, randomized trials comparing LTBI this study was not able to measure the influence of ART on quality
treatment regimens have not included quality of life evaluations, of life.
and it is therefore difficult to report comparisons of the currently Work by Dowdy et al. in Brazil compared 45 HIV-positive adults
available regimens. with 44 individuals with TB and nine with both conditions using
the MOS-HIV and a VAS.40 Similar scores were found in the three
6.2. Extrapulmonary TB groups, with only the physical health summary scores in those
with HIV–TB compared to those with HIV alone being significantly
Distinguishing extrapulmonary from pulmonary TB seems different. In an evaluation of 4900 participants with TB in South
important, although health status is also likely to be related to the Africa, 59% of whom were HIV co-infected, HIV infection was
predominant anatomical site of disease. For example, the impact associated with a significantly lower health status as assessed by
of isolated TB lymphadenitis is likely to be very different to, for the SF-36 (for instance the mean PCS score in those with HIV–TB
instance, TB meningitis. Unfortunately as many studies of quality was 39.4 compared to 42.5 in the HIV-negative patients with TB).
of life in TB have not reported results stratified by disease site, The use of ART was associated with a lower quality of life in the
this is often difficult to quantify. Dhingra and Rajpal reported multivariable analysis, although this did not reach statistical
longitudinal data from a cohort of 51 patients with pulmonary TB significance.41 The interpretation of results concerning ART within
and 25 patients with extrapulmonary TB treated in India22 and such an observational study is not straightforward, as individuals
identified a lower quality of life score in those with extra- with worse immunocompromise (who might be expected to have a
pulmonary TB, despite the fact that several questions in the reduced quality of life) are generally more likely to be offered ART.
instrument used were specific to pulmonary disease. Conversely,
Chamla reported from China no significant difference in SF-36 6.4. Quality of life in MDR-TB
score in those with pulmonary and extrapulmonary TB,25 but no
details on the numbers with extrapulmonary TB or their sites of The complexity and duration of treatment, high rates of adverse
disease were provided. In summary, the paucity of evidence events, additional stigmatization, and difficulties with family life,
regarding quality of life in extrapulmonary TB means that we are fertility, and employment would imply that quality of life will be
still, by and large, at a level where we assume that some forms of particularly impaired in those with MDR and extensively drug-
extrapulmonary TB are associated with significant morbidity and resistant (XDR) TB.42 Globally, an estimated 5% of TB is MDR,
long-term disability, although we have little evidence to confirm representing around 480 000 cases in 2013. This is unevenly
or refute this. distributed, with particularly high rates in some regions resulting
in specific challenges in these areas.10
6.3. HIV–TB co-infection Perhaps because of the high mortality associated with MDR-
TB,43 especially in regions where many patients also have HIV co-
An estimated 13% of those with TB also have an HIV infection.10 infection,44 less attention has been given to quality of life
The combination of these two conditions, both often subject to evaluation in these populations and very little evidence is available
significant stigmatization, is of particular importance.36 TB–HIV in those with MDR-TB. In one of the few reports available, Godoy
co-infection presents unique challenges and could be expected to et al. utilized the AQ20 to measure respiratory symptoms in
have significant implications for quality of life. Unfortunately, 18 patients who had completed at least 18 months of treatment for
many studies have either excluded those with HIV infection, or MDR-TB in Brazil, alongside comprehensive respiratory assess-
have not reported the HIV status of their subjects, and few have ment including the 6-minute walk test, lung function tests, and
specifically evaluated this question. The impact of antiretroviral chest radiographs.45 They reported a reduction in AQ20 score
therapy (ART) usage also needs to be accounted for. (higher scores indicating worse symptoms), but there was a very
Babikako et al. explored quality of life using a translated and wide range (from 0 to 18, maximum = 20), and the relationship
culturally adapted version of the 35-item Medical Outcomes Study between these scores and the physical disabilities of the
instrument in Uganda in 133 patients with pulmonary TB, 50% of participants was not reported. In addition, it should be noted that
whom were HIV co-infected.37 This cross-sectional study selected this instrument was designed to be utilized in asthma and its use in
participants from both public and private hospital settings who the context of TB has not been validated.
were either starting anti-TB treatment or had completed 2 or Treatment regimens for MDR-TB involve many months of
8 months of therapy. It demonstrated significant improvements complex drug combinations, including extended periods with
with treatment: for instance mean visual analogue scale (VAS) injectable medications. These regimens are associated with
scores were 60.7, 67.1, and 78.5 at baseline, 2 months, and significant adverse effects, in particular irreversible hearing loss
8 months, respectively. There was no significant difference in and symptomatic peripheral neuropathies, which affect a signifi-
quality of life in those with and without HIV co-infection, although cant proportion of patients treated for MDR-TB, even with careful
 J. Brown et al. / International Journal of Infectious Diseases 32 (2015) 68–75 73

management.46–48 It is perhaps unsurprising that MDR-TB is 8 quality-adjusted days for the hospitalized period of treatment
associated with high rates of psychological comorbidity – plus 18 quality-adjusted days over a 6-month course of
symptoms of anxiety and depression being present in many treatment.59 This would appear to underestimate the real impact
patients. Furthermore, hospitalization, stigma, and difficulties in of TB disease for many in both the short and long term.27
maintaining family life mean that people with drug-resistant TB Some health status evaluations have assumed that the quality
often become socially isolated and lose the support networks that of life in those with cured TB returns to that of healthy subjects,
are key to the maintenance of health status. whilst others have allocated an arbitrary value for long-term ill-
In addition to the medication used to manage MDR-TB, the health following TB. This is problematic: a study of TB patients in
delivery of services has a major impact on outcome and hence Texas incorporating the effect of chronic pulmonary sequelae of TB
quality of life. Many health systems have responded to MDR-TB in an assessment of QALYs lost to TB suggested that only 4% of the
with models of care that have included prolonged periods of total lost QALYs result from acute TB morbidity, whilst mortality
hospitalization. Of note here, organized ambulatory care appears accounted for 18% and chronic morbidity following TB was
to have at least equivalent long-term outcomes49 and may also responsible for 78% of the lost QALYs.60
result in improved quality of life, although studies reporting health An alternative strategy to the use of QALYs is the calculation of
status using alternative models of care are limited.49 DALYs, which requires the addition of years lost to disability and
years lost to premature death. Disability weights are calculated
6.5. TB infection and quality of life in children and other high-risk using population surveys in which participants allocate prefer-
groups ences to different hypothetical health states, such as that used for
the Global Burden of Disease Survey (which draws on responses
An estimated 550 000 children developed TB in 2013.50 In from over 30 000 people61). However, as demonstrated by Diel and
addition, TB affecting parents and care-givers has a significant Lampenius, the combination of more specific epidemiological data
impact on the quality of life of children, particularly as it tends to and statistical modelling methods may yield more accurate (and in
affect those of working and childbearing age. However, there has this case higher) estimates for DALYs lost.62 Remaining uncertain-
been little structured evaluation of these effects: the systematic ties surrounding several parameters required for these calculations
review of the literature up to 2011 by Bauer et al. could not identify mean that this is at best an estimate (and such an assessment for
any studies that included participants under the age of 11 years.5 regions where less complete data exist will necessarily be less
Other specific groups of individuals at risk of TB are worthy of accurate).
consideration: extremely high rates of TB infection are reported in
specific groups in some settings, for instance health-care work- 8. Conclusions and suggestions for future work
ers51–53 and prisoners.54 TB is increased in pregnancy and the
postpartum period,55 and is associated with adverse obstetric In summary, current evidence regarding the quality of life
outcomes.56 The inclusion of the impact of TB in such specific associated with TB, its treatment, and long-term impact is limited.
groups would be necessary, therefore, for the comprehensive Collecting meaningful data on HRQOL in TB presents several
evaluation of the impact of TB on HRQOL, but to date this has not challenges (see Table 4 for suggestions of what a hypothetical ideal
been done. study of quality of life in TB would include). However, the collection
of quality of life data in future trials of therapies or preventative
7. Quality of life and cost-effectiveness measures is important, in particular in neglected areas such as the
management MDR-TB, the implications of extrapulmonary TB, and
An assessment of the cost-effectiveness of healthcare inter-
ventions is important for the rational allocation of resources. Such
evaluations require the construction of utility weights for a given Table 4
What would be included in an ideal study of quality of life in TB?
condition, to allow the calculation of lost quality-adjusted life-
years (QALYs) or disability-adjusted life-years (DALYs) associated Study feature Characteristics
with TB. The calculation of QALYs requires the allocation of a single Instrument(s) Able to capture all health-related physical impairment
utility measure based on patient-level assessments such as those (i.e., not organ- or system-specific)
discussed above. One year in perfect health is equal to 1 QALY, and Able to evaluate psychological morbidity associated with
when a utility weight is applied this allows adjustment for reduced TB
Culturally and linguistically appropriate for the study
quality of life associated with a particular condition or health state. population
For example a year spent with a condition associated with ‘half’ Includes evaluation of social role limitations and stigma
normal health would be worth 0.5 QALYs. There are few current Simple to administer
studies that provide data to assist with this. The incomplete Repeatable over time
Study population Representative of the population at risk of TB, including,
assessment of the effect of TB on quality of life, described earlier,
as far as possible, groups that are often neglected (e.g.,
may have led to a systematic underestimation of the impact of TB HIV-positive individuals, children, pregnant women, and
in lost QALYs. This has important public health policy implica- hard to reach groups such as the homeless and those with
tions.57 substance abuse problems)
As the mortality associated with TB in developed countries is Study design Prospective design with data collection at defined time-
points (e.g., baseline, end of intensive phase of treatment,
low (6.6% in the European region in 201232), failure to quantify the end of treatment, and defined follow-up point)
long-term effects of TB on quality of life would lead to an Includes evaluation of residual impairment in quality of
underestimation of lost QALYs. Studies attempting to assign values life after treatment and change in health-related quality
for lost adjusted life expectancy associated with TB have used of life after a period of follow-up
Reporting of results Includes a description of the following parameters: site of
differing methodologies and yielded variable results. Work by
disease, age, gender, ethnicity, and HIV status of
Tsevat et al. in 1998, which continues to be cited as a source of participants
utility weights for health economic analyses, based quality of life Includes analyses of comorbidities (such as diabetes,
adjustments on ‘‘a consensus of internists in our division’’ and renal failure, and HIV) and cofactors (such as smoking and
resulted in a deduction of only 7 days of quality-adjusted life for socioeconomic status) that may influence quality of life

non-fatal TB.58 Similarly Porco et al. calculated there to be only TB, tuberculosis.
74 J. Brown et al. / International Journal of Infectious Diseases 32 (2015) 68–75

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